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. 1995 Jul;40(4):241–250. doi: 10.1007/BF01519898

Interleukin-6 involvement in mesothelioma pathobiology: inhibition by interferon α immunotherapy

H Bielefeldt-Ohmann 1,2,✉, A L Marzo 1, R P Himbeck 1, A G Jarnicki 1, B W S Robinson 1, D R Fitzpatrick 1
PMCID: PMC11037711  PMID: 7750122

Abstract

A role for interleukin-6 (IL-6) in malignant mesothelioma has been suggested by the clinically presenting symptoms of mesothelioma patients, which include fever, weight loss and thrombocytosis. A murine model of malignant mesothelioma was therefore used to examine the potential role of IL-6 in this cancer type and whether the effect of interferon α (IFNα) therapy on mesothelioma might be mediated, in part, by regulating IL-6 levels and/or IL-6-induced pathobiology. A panel of human and murine mesothelioma cell lines was assayed for endogenous IL-6 production in a bioassay, and for IL-6-mRNA expression. Four out of 5 human and 5 out of 15 murine mesothelioma cell lines produced moderate to high levels of bioactive IL-6 in vitro. This result was corroborated by mRNA detection. One of the representative murine cell lines, AB22, was chosen for further in vivo studies in the murine mesothelioma model. In AB22-inoculated mice detectable serum IL-6 levels were found to precede macroscopically detectable tumour growth, clinical signs (cachexia, abdominal distension, diarrhoea) and changes in the peripheral lymphoid organs (cell depletion and functional depression). Treatment with anti-IL-6 antibody curtailed the clinical symptoms (P<0.001), as did treatment with recombinant human (rhu) IFNα (P<0.001). Neither anti-IL-6 antibody nor rhuIFNα had a direct growth-inhibitory effect on the AB22 mesothelioma cell line in vitro, however, in vivo rhuIFNα treatment of mice inoculated with AB22 cells attenuated both IL-6 mRNA expression in the tumours and serum IL-6 levels, ameliorated the depression of lymphocyte activities, and enhanced the number of tumour-infiltrating lymphocytes and macrophages. On the basis of these results it is suggested that IL-6 mediates some of these effects, directly or indirectly, and that a combination therapy of rhuIFNα and anti-IL-6 antibody may be an improved palliative treatment for patients with malignant mesothelioma.

Key words: Mesothelioma, IL-6, Cancer cachexia IFNα Immunotherapy

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